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Hypoxia promotes 786-O cells invasiveness and resistance to sorafenib via HIF-2α/COX-2

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Abstract

Accumulating evidences indicated that hypoxia-induced factors and COX-2 play a important role in tumorigenesis in various human cancer. Yet, the relationship between HIFs and COX-2 in human renal cancer remains unclear. The present study was to examine the role of HIFs and COX-2 in the invasiveness and the resistance to target agent in renal cancer cell line (786-O). In 786-O cells, hypoxia induced the increase in the protein expression of HIF1 and HIF2. We also demonstrate that hypoxia up-regulated the protein expression of COX-2 and Snail, but down-regulation of E-cadherin expression in 786-O cells promoted the invasiveness of 786-O cells and enhanced the resistance of 786-O cells to sorafenib. siRNA target to HIF1α, HIF2α and NS398, a selective inhibitor of COX-2, were used in this study. Only siRNA-HIF2α significantly suppressed the protein expression of HIF2 and COX-2, then decreased the invasive ability and resistance of 786-O cells to sorafenib under hypoxia. NS398 attenuated the increase in invasive cells number and the IC50 value of sorafenib induced by hypoxia. In conclusion, our results demonstrated that hypoxia promoted the invasiveness and resistance of 786-O cells to sorafenib via HIF2 and COX-2 and induced the activation of Snail/E-cadherin, suggesting that a signalling mechanism involving HIF2/COX2 modulates invasiveness and resistance to sorafenib in 786-O cells under hypoxia.

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Acknowledgments

We thank the staff of Life Science Institute laboratory for helping technical assistance.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China

    Chun-Xiong Zhao & Xiao-Hou Wu

  2. Department of Laboratory Medicine, Chongqing Medical University, Yi Xue Yuan Road, Chongqing, China

    Chun-Li Luo

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  1. Chun-Xiong Zhao
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Correspondence to Xiao-Hou Wu.

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Zhao, CX., Luo, CL. & Wu, XH. Hypoxia promotes 786-O cells invasiveness and resistance to sorafenib via HIF-2α/COX-2. Med Oncol 32, 419 (2015). https://doi.org/10.1007/s12032-014-0419-4

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